DNA-based aptamers for human cathepsin G
The present research is directed to the identification of non-peptidic inhibitors of cathepsin G characterised by high levels of selectivity and which can be efficaciously used in the treatment and prophylaxis of inflammatory occurrences and procoagulant conditions. The cathepsin G-inhibiting aptamers according to the invention consist of linear DNA or polynucleotide sequences having a chain length of at least 60 nucleotides and being substantially not subjected to undergo efficient base pairing.
1. A method for the treatment of a disease selected from the group consisting of inflammatory occurrences, procoagulant conditions, genetic diseases, degenerative diseases, DNA damages, neoplasia and skin diseases, which comprises administering to a patient in need thereof cathepsin G-inhibiting aptamers consisting of linear DNA or polynucleotide sequences having a chain length of 60-120 nucleotides and undergoing inter and/or intra molecular base pairing to an extent lower than 20%, said sequences being characterized by:
being (GT) n or (AC) n oligopolymers in which n is in the range from 30 to 60.
2. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers have a chain length of 70-110 nucleotides.
3. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers have a chain length of 80-100 nucleotides.
4. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers are single stranded sequences.
5. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers have a molar content in guanine of 25-50%.
6. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers have a molar content in guanine of 35-45%.
7. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers are (GT) n or (AC) n oligopolymers in which n is in the range from 35 to 60.
8. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers undergo inter and/or intra molecular base pairing to an extent lower than 10%.
9. The method of claim 1 , wherein said cathepsin G-inhibiting aptamers undergo inter and/or intra molecular base pairing to an extent lower than 5%.
10. The method of claim 1 , wherein said disease is an inflammatory disease.
11. The method of claim 7 , wherein said cathepsin G-inhibiting aptamers are (GT) n or (AC) n oligopolymers in which n is in the range from 40 to 50.